Cordillera Regional Science High School was originally known as Regional Science High School for the Cordillera Administrative Region (RSHS-CAR). The school is among the eleven regional science high schools established in the country in the school year 1994-1995 by virtue of DECS Order No. 69, s. 1993. In 1997, it gained its independence from its mother school, Benguet National High School, through the Republic Act No. 8376 or "The act establishing the Cordillera Regional Science High School in La Trinidad, Benguet and Appropriating Funds Thereof," which was authored by former congressman Ronald M. Cosalan, recieving approval on November 13, 1997. From June 1994 to December 1998, CRSHS has been using the Benguet School Teacher's Association (BSTA) building in the Barangay hall & warehouse at the Benguet National Highschool-Puguis Annex for its first classes. On January 4, 1999 CRSHS transferred to its present site in Upper Wangal, which was donated by the Provincial Government of Benguet. Since then, it has been under the auspices of the Department of Education.

CRSHS first started with 86 first-year students in the 1994-1995 school year. The population of the school has grown since and in 2004, it has hundreds of students with a maximum of 35 students per class. All students who enter CRSHS must pass the qualifying examinations before enrollment. In June 2016, the school welcomed its first senior high school students.
From the outset CRSHS met two definitions of a special mathematics and science school: it offers advanced subjects in mathematics and science and beyond the regular curriculum for public high schools and emphasis on scientific research.

One special feature of CRSHS is its emphasis on mathematics and science curriculum coupled with its use of Information and Communications Technology (ICT) resources, it has rigorous coverage in a variety of topics including earth and environmental science; technical writing; research analytic geometry; calculus; pre-calculus; advanced calculus; advanced chemistry; and robotics for the junior high school division. For the senior high school, CRSHS offers the Science, Technology, Engineering, and Mathematics (STEM) strand under the academic track.

Through the collaboration of stakeholders, numerous school based innovations were introduced to help students, teachers, and parents. Among them were Digital Literacy for Parents Program (DLLP); Robotics for second-year students; Young Math Wizard Contest for grade six pupils; Speak, Think and Argue In Reading (STAR); Global Peer Dialogue Network; Students' Evaluation for Teachers and Service-Learning; and many others. Apart from the DepEd recognized organizations, the school has its own organized clubs: Glee Club for music enthusiasts and Arts Guild for artistic talents.

Cordillera Regional Science High School (CRSHS) has played a leading role in the field of mathematics and science education in the region especially in environmental preservation through its participation in research for the "Save Balili River" project.

The school has gained recognition internationally having been conferred with three (3) awards in the International Earth Science Competition in 2008. It has also reaped recognition in the National Science Fair, Robotics, National Schools Press Conference, Metrobank DepEd MTAP Math challenge, Palarong Pambansa, and the Student Technologists and Entrepreneurs of the Philippines (STEP)-ICT contest.

The school's Glee Club also went on to snatch the 3rd place In the National Festival of Talents 2018. Further, the Glee Club hauled 3 gold medals in 8th Bali International Choir Festival in July 2019, becoming the first-ever high school choir from the Cordillera that represented the country in an international choral competition.

Aside from the students winning these competitions, teachers excelled in their own field and have won several competitions such as RSHS Summit contests in action research and the use of ICT in mathematics and science; SMART Mentor, Microsoft, Innovative Teachers Leadership Award (ITLA): Regional Level Outstanding, Supreme Student Government (SSG) Adviser, Regional Level Outstanding Mentor (English) and Outstanding School Paper Adviser - National Awardee (Filipino).

Furthermore, CRSHS has free Wi-Fi zones (60 mbps) with three science laboratories - Biology, Chemistry, and Physics. The school currently houses five buildings for classroom use.

Keeping up with the school's vision to be a wellspring of excellent math and science education, the school continues to expand its networks to the alumni association and other private and non-government organizations for resources to create the best environment that would support wholesome learning and work environments.